Association of Sjögren’s syndrome with myotonic dystrophy type 1

Abstract

A 47-year-old woman presented with sicca symptoms, polyarthralgias, polymyalgias and dysphagia. She was found to have positive antinuclear, anti-SSA-Ro and anti-SSB-La antibodies. Slit lamp exam confirmed the presence of keratoconjunctivitis sicca, and the patient was diagnosed with Sjögren’s syndrome. Three years later, she was referred for evaluation of gait instability associated with recent falls. On physical examination, the patient was found to have bilateral ptosis, percussion myotonia, distal upper and lower extremity weakness, and a steppage gait. Electromyography demonstrated electrical myotonia. Genetic testing revealed expanded CTG repeats (733 and 533) in the myotonic dystrophy type 1 (DM1) protein kinase gene, confirming the diagnosis of DM1. Dysphagia, pain and eye discomfort may occur in both Sjögren’s syndrome and DM1, and in this case, may have delayed the diagnosis of muscular dystrophy.

Background

Sjögren’s syndrome and myotonic dystrophy type 1 (DM1) are both multisystem diseases. Sjögren’s syndrome is a chronic autoimmune disease characterised by dry eyes, dry mouth, polyarthralgias and fatigue, as well as neurological, haematological and pulmonary abnormalities. DM1 is the most common form of adult-onset muscular dystrophy, with cardinal features of weakness and myotonia. It is also associated with multisystem dysfunction affecting the heart, eye, brain, gastrointestinal tract and endocrine system. In both conditions, dysphagia, pain and eye involvement are common.

Case presentation

A 47-year-old woman was referred to a rheumatologist for evaluation of joint pain. She complained of hand arthralgias and lower extremity pain, and admitted to dry eyes and mouth, dysphagia and Raynaud’s phenomenon. She mentioned that she fell occasionally. Ophthalmological exam confirmed the presence of keratoconjunctivitis sicca, and the patient was diagnosed with Sjögren’s syndrome. Slit lamp exam revealed punctate epithelial erosions, as well as corneal guttata and a beaten-bronze appearance of the corneal endothelium, consistent with Fuchs endothelial corneal dystrophy (FECD).

Three years later, the patient was referred to a neurologist for evaluation of gait instability. She reported progressively worsening ataxia, associated with recent falls and difficulty maintaining an upright posture. Her hands and arms had recently become weak, and she had difficulty grasping objects, opening jars, pulling open drawers and operating scissors. The patient also complained of hip and knee pain, as well as sleep dysfunction. In addition, she reported that physicians and family members had suggested that her speech was slurred, although she did not appreciate any change. On physical examination, she was found to have lingual dysarthria, bilateral ptosis, percussion myotonia, distal upper and lower extremity weakness, and a steppage gait. She was areflexic.

The patient had a previous medical history of asthma/emphysema, a ‘heart attack’ at age 30 years, and IgG-lambda monoclonal gammopathy of unclear significance. She also had cataracts, for which she underwent surgery. One of her sisters has hyperthyroidism; the other has hypothyroidism. In retrospect, her daughter and a sister appear to have the same muscle disease she has, but they have not undergone genetic testing.

Because of the patient’s reported history of a heart attack at a young age, she was referred to a cardiologist. Electrocardiogram (EKG) was normal, and echocardiogram showed normal left ventricular wall motion and ejection fraction, and mild to moderate mitral regurgitation. The myocardial infarction years prior was ascribed to cocaine use.

Investigations

Laboratory evaluation at initial presentation to the rheumatologist revealed leucopenia, anaemia and borderline thrombocytopenia. Erythrocyte sedimentation rate was 95 mm/hour. Thyroid-stimulating hormone was normal. Immunological testing revealed a positive antinuclear antibody at 1:640 speckled, anti-SSA-Ro >8 antibody index (AI), anti-SSB-La >8 AI, rheumatoid factor elevated at 63.1 IU/mL, negative Sm, negative RNP, double stranded DNA of 11.4 IU, negative centromere and Scl-70, normal C3, reduced C4 (16 mg/dL), negative cryoglobulins and a negative comprehensive antiphospholipid panel. IgG4 was normal, and hepatitis C and HIV testing were negative. Creatine kinase (CK) was normal.

The neurological evaluation included needle electromyography (EMG), which showed prominent myotonic discharges in the left tibialis anterior, without diffuse polyneuropathy. A videoesophagram showed esophageal dysmotility with transient reverse peristalsis. A barium pill lodged in the left vallecula, suggestive of neuromuscular dysphagia.

Genetic testing revealed expansion of the CTG repeat sequence in the DMPK gene (733 and 533 repeats in the two alleles, where normal is <36 repeats), confirming the diagnosis of DM1.

Differential diagnosis

The differential diagnosis at initial presentation to the rheumatologist included Sjögren’s syndrome, systemic lupus erythematosus, scleroderma and undifferentiated connective tissue disease. Other diagnoses considered to account for the patient’s polymyalgias and polyarthralgias included viral infection, hypothyroidism and fibromyalgia. Further evaluation revealed that the patient met American College of Rheumatology/European League Against Rheumatism criteria for Sjögren’s syndrome.¹

When seen by the neurologist 3 years later because of frequent falls, a diagnosis of myotonic dystrophy was proposed based on the presence of distal weakness, temporal wasting, cataracts, sleep dysfunction and clinical myotonia. EMG confirmed the presence of electrical myotonia. In a patient with distal weakness but without myotonia or the systemic features characteristic of DM1, the differential diagnosis includes a large number of inherited distal myopathies, various forms of hereditary motor neuropathy (or distal spinal muscular atrophy), hereditary motor sensory neuropathies (many classified as subtypes of Charcot-Marie-Tooth disease) and other chronic neuropathies.

Treatment

The patient’s dry eyes were treated with artificial tears, cyclosporine eye drops and punctal plugs, with improvement in symptoms. She was started on hydroxychloroquine 400 mg per day for polyarthralgias, but developed a pruritic rash, so it was discontinued due to a presumed drug allergy.

In addition, the patient received physical therapy for her myotonic dystrophy. She was advised to eat a soft, mechanical diet. She was provided with a continuous positive airway pressure mask to sleep.

Outcome and follow-up

The patient has been followed for 9 years since her diagnosis of Sjögren’s syndrome. She continues to use artificial tears and cyclosporine eye drops. Six months ago, she fell and sustained a non-displaced patellar fracture. She is seen by a home health aide three times a week, as well as by a home physical therapist. When she goes outside she uses a rolling walker and ankle foot orthoses. She feels more stable with the rolling walker.

Discussion

To the best of our knowledge, this is the first reported case of Sjögren’s syndrome occurring in association with DM1. Autoantibodies have previously been reported in association with myotonic dystrophy, with 10 of 24 patients being found to have antismooth muscle antibodies.² An association between autoimmune disease and myotonic dystrophy type 2 (DM2) has also previously been reported, although only one case of Sjögren’s syndrome was observed.^3–6 The frequency of autoimmune diseases and autoantibodies was noted to be significantly higher in patients with DM2 compared with DM1, with only one patient in the DM1 group having an autoimmune disease (Crohn’s disease).³

It is important to be aware of the possible association between Sjögren’s syndrome and DM1 because several of the symptoms of the two diseases are similar, and the conditions can occur contemporaneously. Because they are multisystem disorders, the myotonic dystrophies are unique among the muscular dystrophies. The muscular symptoms of DM1 include myalgias, myotonia and weakness affecting craniobulbar and distal limb muscles. Manifestations in other systems include cardiac arrhythmias, cognitive impairment, endocrine disturbances, gastrointestinal dysmotility, sleep disorders, cataracts, polyneuropathy, hypogammaglobulinemia and increased susceptibility to malignancy.⁷ The non-muscular symptoms contribute greatly to morbidity and mortality in DM1 patients. It has been reported that the diagnostic delay in DM1 can range from 8 to 15 years,⁸ likely due to the heterogeneity of patient complaints. Overlapping symptoms in DM1 and Sjögren’s may include dysphagia, myalgias, polyneuropathy and ocular dysfunction. Although dysphagia in Sjögren’s syndrome is often attributed to mucosal dryness, it may also result from pharyngeal dysfunction, abnormal esophageal peristalsis, loss of dentition, cricoarytenoid joint arthritis, neuropathy, esophageal abnormalities or gastro-oesophageal reflux.⁹ In contrast, dysphagia in DM1 has been attributed to reduced upper esophageal sphincter resting pressure and decreased pharyngeal contraction amplitude.¹⁰

Pain is a symptom of both Sjögren’s syndrome and DM1. Patients with Sjögren’s syndrome typically complain of arthralgias, whereas those with myotonic dystrophy more often report myalgias. However, patients often have difficulty localising their pain. Our patient presented with both polyarthralgias and polymyalgias. The diagnosis of her myotonic dystrophy may have been delayed because her symptoms of dysphagia and pain were attributed to autoimmune disease. The bias of the particular specialist evaluating a patient may contribute to a delay in diagnosis of a condition outside their field.

While the association of Sjögren’s syndrome with myotonic dystrophy is rare, at least 10–20% of patients with Sjögren’s syndrome will exhibit involvement of the peripheral nervous system. Neurological manifestations include mononeuropathy multiplex, sensory neuronopathy, autonomic neuropathy and polyneuropathy, which may preferentially affect small fibres.¹¹ Muscle biopsy may show inflammatory changes, though clinical myositis is uncommon, and CK is usually normal.¹²

Ocular symptoms in Sjögren’s syndrome and myotonic dystrophy may also be similar. Interestingly, FECD has been described in patients with DM1, and was present in our patient.¹³ Patients with FECD may complain of a sensation of grittiness or pain in the eyes, which may be similar to the ocular symptoms of a Sjögren’s syndrome patient.

Learning points.

• Sjögren’s syndrome and myotonic dystrophy type 1 (DM1) are both multisystem diseases.

• Symptoms of Sjögren’s syndrome can overlap with those of DM1, but neuromuscular symptoms in patients with Sjogren’s syndrome are more likely related to neuropathy or perhaps myositis.

• Both Sjögren’s syndrome and DM1 patients may experience dysphagia, pain and ocular discomfort.

• Sjögren’s syndrome and DM1 may coexist.